Our studies of various virologic and immunopathologic processes that occur when viruses replicate in the ocular microenvironment comprise four areas: (1) coronavirus infection in ocular and optic nerve cells, (2) the possible roles of viruses in human diseases, (3) antiviral therapeutic actions of cytokines and drugs, and (4) molecular diagnosis and pathogenesis of cytomegalovirus (CMV) infections in man. We have established that murine coronavirus can induce ocular disease and may be used as a model system for studying retinal degenerative diseases. This model has many unique features. The virus is capable of inducing an acute infection in the presence of mild retinal vascular inflammation. Initial retinal damage is followed by clearance of the virus and progressive retinal degeneration, even months after the virus is gone. The virus replicates predominantly in Muller cells and also can be detected in retinal pigment epithelium (RPE) and photoreceptor cells. Recent studies show that there are genetic and immunologic components to this disease. The retinal degenerative pathologic manifestations of the disease can be influenced by the genetics of the host, ie, some strains of mice are resistant to virus-induced retinal degenerative changes. The pathologic changes also are closely related to the development of antiretinal and anti-RPE antibodies. These findings suggest a role for autoimmunity in the pathogenesis. This disease may be considered a model for degenerative diseases of the pigment epithelium and photoreceptors in humans. The need for effective drug treatment and prevention of herpes virus and other viral diseases has assumed growing importance. We found that leukoregulin, a naturally occurring immunologic cytokine, not only increases the antiviral actions of the drug acyclovir but also directly inhibits herpes simplex virus replication, demonstrating that combination immunotherapy and chemotherapy can produce substantial inhibition of herpes virus replication and providing a rationale for applying this approach to treating virus infections. Studies initiated this past year indicate that CMV is capable of replicating within human RPE cells in vitro; however, replication is limited at the level of immediate early protein production. The low frequency of expression of immediate early viral proteins in RPE cells and the subsequent slow replication of CMV may be critical variables in terms of their relationship to viral persistence and activation within the retina.